Baboons and vervet monkeys will be subjected to controlled manipulations simulating human risk factors for the atherosclerotic diseases to induce experimental atherosclerosis. The roles of multiple genetic and environmental factors will be examined in the intact animal. Emphasis will be placed on the interactions of these variables in infancy on atherogenesis in the adolescent and young adult. Experiments with baboon infants reared to maturity will examine the effects of infant nutrition, plant sterols and polyunsaturated fats in the diet, and total caloric intake on atherosclerosis. Metabolic studies in infants and juveniles will examine the relationship of dietary carbohydrate to fat metabolism, and the relationship of abnormal carbohydrate metabolism to atherogenesis. The role of intestinal microflora in cholesterol metabolism will be studied in conventional and gnotobiotic baboons. The heritability of characters associated with atherosclerosis will be determined by selective breeding and by hybridization. In animals made hypertensive while on an atherogenic diet, the pathophysiology of hypertension and the effects of the mode of antihypertensive therapy on atherogenesis will be investigated. To develop other models of hypertension, the possibility of producing hypertension by operant conditioning or by salt loading in infancy will be explored. Operant conditioning will be used to induce baboons to inhale cigarette smoke to study the effects of cigarette smoking, alone and combined with stress, on atherosclerosis and pulmonary physiology. Experiments will be performed to determine the effects of carbon monoxide and nicotine derived from cigarette smoke on atherogenesis. The relationship of a psychosocial stress, social mobility to atherosclerosis will be studied. The effects of various experimental regimens on selected coagulation factors and on platelets also will be studied.